Familial Alzheimer disease(FAD)-associated presenilin forming _Y-secretase complex mediates dual transmembraneous cleavage of amyloid precursor protein(APP) (_Y40/42 and _Y49) as well as Notch protein (S3 and S4). APP has an amino acid valine just before _Y40 site (residue 40) and after _Y49 site (residue 50) and the cleavage variety of _Y40/42 is greater than _Y49. In order to investigate the effect of valine upon S4 cleavage site as well as _Y-secretase cleavage, we individually replaced transmembrane domain residue of Notch-1 protein with valine. We observed that all valine-mutated Notch-1 protein have a dominant cleavage site between 1731 and 1732 (S4 site) with slight variations, suggesting that valine does not have major role in _Y-secretase cleavage.We hypothesized that aluminum may modulate cell viability, axonal transport and neurite outgrowth in APP/PS mutant-bearing cells. Apoptosis was induced Aluminum-maltol treatment in a dose-dependent manner in all cell lines. The APP mutation-bearing cell lines showed significant induction of apoptosis compared to that of wild-type cells. We concluded that aluminum alters cell viability and the axonal transport system in FAD pathogenic mutation-bearing cells.